MARS: Nye mekanismer for genaktivering gjennom oppheving av SUMO-mediert represjon av transkripsjon

Modification of proteins with small ubiquitin-related modifiers (SUMOs) is now established as one of the key regulatory modifications in eukaryotic cells, significantly affecting fundamental nuclear processes such as transcription and chromatin organization. A large number of transcription factors and cofactors are SUMO-modified, which in most cases are associated with repression. One implication of this potent repressive mechanism is that relief of SUMO-mediated repression may represent a significant contribution to gene activation. This derepression is still poorly understood and is the subject of the current proposal. By focusing on targeting of SUMO-proteases, link to chromatin remodeling and role in controlling pioneer transcription factors, we aim to unravel novel mechanisms of gene activation based on the con-trolled relief of SUMO-mediated repression of transcription. We will use the transcription factor c-Myb as model, as we have shown that c-Myb is a sensitive target for SUMOylation, recruiting chromatin re-modelers and having properties suggesting a role as pioneer transcription factor.

In addition to the project manager, Odd Stokke Gabrielsen, with broad knowledge of the c-Myb and SUMO field, key collaborators are Ragnhild Eskeland, a young investigator with expertise in epigenet-ics, and an international renowned expert in stem cells and c-Myb biology, Jon Frampton, professor at University of Birmingham.